PSD-95 Is Associated with the Postsynaptic Density and Not with the Presynaptic Membrane at Forebrain Synapses

PSD-95, a prominent protein component of the postsynaptic density (PSD) fraction from rat forebrain, has been localized by light microscopy to dendrites of hippocampal neurons (Cho et al., 1992) and to the presynaptic plexus of cerebellar basket cells (Kistner et al., 1993). Here we extend these studies to show that an affinity-purified antibody to PSD-95 labels the dendrites of most neurons in the forebrain and of a subset of neurons in the cerebellum. To confirm that PSD-95 is associated with the PSD at forebrain synapses and to clarify whether it is also associated with the presynaptic membrane, we employed immunogold electron microscopy of forebrain synaptosomes. Gold-labeled antibodies to PSD-95 labeled postsynaptic densities in both intact and lysed forebrain synaptosomes but did not label presynaptic terminals or the presynaptic membrane. The asymmetric distribution of PSD-95 at synapses contrasts with that of its homologs, disks-large and ZO-1, which are arranged symmetrically at septate and tight junctions, respectively

Wave shapes in alternating DSC

ADSC with its periodical temperature programs combines the features of DSC measured at high heating rate (high sensitivity) with those at low heating rate (high temperature resolution). In addition, the "reversing” cp effects can be separated from the "non-reversing” latent heat effects. Various periodical temperature programs can be applied. This paper compares the different possible temperature programs and their algorithms for the cp determination for metal, metal oxide and polymer of various properties. Simulated and measured results for various wave shapes and samples are presented. The relevant sample properties and their influence on the measurements are identified and guiding rules for the proper choice of the various experimental parameters are given. Measurements with different samples, performed with the new METTLER TOLEDO STARe-System, are shown and compared with the simulation results. The simulations and the measurements clearly show that the alternating techniques can yield new information about sample properties, but are susceptible to the proper choice of the various experimental parameter

C-Terminal truncation of NR2A subunits impairs synaptic but not extrasynaptic localization of NMDA receptors

NMDA receptors interact via the extended intracellular C-terminal domain of the NR2 subunits with constituents of the postsynaptic density for purposes of retention, clustering, and functional regulation at central excitatory synapses. To examine the role of the C-terminal domain of NR2A in the synaptic localization and function of NR2A-containing NMDA receptors in hippocampal Schaffer collateral–CA1 pyramidal cell synapses, we analyzed mice which express NR2A only in its C-terminally truncated form. In CA1 cell somata, the levels, activation, and deactivation kinetics of extrasynaptic NMDA receptor channels were comparable in wild-type and mutant NR2A^(ΔC/ΔC) mice. At CA1 cell synapses, however, the truncated receptors were less concentrated than their full-length counterparts, as indicated by immunodetection in cultured neurons, synaptosomes, and postsynaptic densities. In the mutant, the NMDA component of evoked EPSCs was reduced in a developmentally progressing manner and was even more reduced in miniature EPSCs (mEPSCs) elicited by spontaneous glutamate release. Moreover, pharmacologically isolated NMDA currents evoked by synaptic stimulation had longer latencies and displayed slower rise and decay times, even in the presence of an NR2B-specific antagonist. These data strongly suggest that the C-terminal domain of NR2A subunits is important for the precise synaptic arrangement of NMDA receptors

The Influence of the Degree of Heterogeneity on the Elastic Properties of Random Sphere Packings

The macroscopic mechanical properties of colloidal particle gels strongly depend on the local arrangement of the powder particles. Experiments have shown that more heterogeneous microstructures exhibit up to one order of magnitude higher elastic properties than their more homogeneous counterparts at equal volume fraction. In this paper, packings of spherical particles are used as model structures to computationally investigate the elastic properties of coagulated particle gels as a function of their degree of heterogeneity. The discrete element model comprises a linear elastic contact law, particle bonding and damping. The simulation parameters were calibrated using a homogeneous and a heterogeneous microstructure originating from earlier Brownian dynamics simulations. A systematic study of the elastic properties as a function of the degree of heterogeneity was performed using two sets of microstructures obtained from Brownian dynamics simulation and from the void expansion method. Both sets cover a broad and to a large extent overlapping range of degrees of heterogeneity. The simulations have shown that the elastic properties as a function of the degree of heterogeneity are independent of the structure generation algorithm and that the relation between the shear modulus and the degree of heterogeneity can be well described by a power law. This suggests the presence of a critical degree of heterogeneity and, therefore, a phase transition between a phase with finite and one with zero elastic properties.Comment: 8 pages, 6 figures; Granular Matter (published online: 11. February 2012

Keck Spectroscopy of Faint 3<z<8 Lyman Break Galaxies:- Evidence for a Declining Fraction of Emission Line Sources In the Redshift Range 6<z<8

Using deep Keck spectroscopy of Lyman break galaxies selected from infrared imaging data taken with WFC3/IR onboard the Hubble Space Telescope, we present new evidence for a reversal in the redshift-dependent fraction of star forming galaxies with detectable Lyman alpha emission in the redshift range 6.3 < z < 8.8. Our earlier surveys with the DEIMOS spectrograph demonstrated a significant increase with redshift in the fraction of line emitting galaxies over the interval 4 < z < 6, particularly for intrinsically faint systems which dominate the luminosity density. Using the longer wavelength sensitivities of LRIS and NIRSPEC, we have targeted 19 Lyman break galaxies selected using recent WFC3/IR data whose photometric redshifts are in the range 6.3 < z < 8.8 and which span a wide range of intrinsic luminosities. Our spectroscopic exposures typically reach a 5-sigma sensitivity of < 50 A for the rest-frame equivalent width (EW) of Lyman alpha emission. Despite the high fraction of emitters seen only a few hundred million years later, we find only 2 convincing and 1 possible line emitter in our more distant sample. Combining with published data on a further 7 sources obtained using FORS2 on the ESO VLT, and assuming continuity in the trends found at lower redshift, we discuss the significance of this apparent reversal in the redshift-dependent Lyman alpha fraction in the context of our range in continuum luminosity. Assuming all the targeted sources are at their photometric redshift and our assumptions about the Lyman alpha EW distribution are correct, we would expect to find so few emitters in less than 1% of the realizations drawn from our lower redshift samples. Our new results provide further support for the suggestion that, at the redshifts now being probed spectroscopically, we are entering the era where the intergalactic medium is partially neutral.Comment: 8 pages, 5 figures, Accepted to ApJ 10/1/1

Scaling in a continuous time model for biological aging

In this paper we consider a generalization to the asexual version of the Penna model for biological aging, where we take a continuous time limit. The genotype associated to each individual is an interval of real numbers over which Dirac $\delta$--functions are defined, representing genetically programmed diseases to be switched on at defined ages of the individual life. We discuss two different continuous limits for the evolution equation and two different mutation protocols, to be implemented during reproduction. Exact stationary solutions are obtained and scaling properties are discussed.Comment: 10 pages, 6 figure

Trends in Cancer-Center Spending on Advertising in the United States, 2005 to 2014

In the United States, cancer centers commonly advertise clinical services directly to the public. Potential benefits of such advertising include informing patients about available treatments and reducing the stigma of cancer.1, 2 Potential risks include misleading vulnerable patients and creating false hopes, increasing demand for unnecessary tests and treatments, adversely affecting existing clinician-patient relationships, and increasing healthcare costs.3, 4 Understanding trends in the advertising spending of cancer centers and the characteristics of the centers that spend the most can inform the debate about the impact of these advertisements. Our hypothesis was that advertising spending has increased and that spending is concentrated among for-profit cancer centers

New Constraints on Cosmic Reionization from the 2012 Hubble Ultra Deep Field Campaign

Understanding cosmic reionization requires the identification and characterization of early sources of hydrogen-ionizing photons. The 2012 Hubble Ultra Deep Field (UDF12) campaign has acquired the deepest infrared images with the Wide Field Camera 3 aboard Hubble Space Telescope and, for the first time, systematically explored the galaxy population deep into the era when cosmic microwave background (CMB) data indicates reionization was underway. The UDF12 campaign thus provides the best constraints to date on the abundance, luminosity distribution, and spectral properties of early star-forming galaxies. We synthesize the new UDF12 results with the most recent constraints from CMB observations to infer redshift-dependent ultraviolet (UV) luminosity densities, reionization histories, and electron scattering optical depth evolution consistent with the available data. Under reasonable assumptions about the escape fraction of hydrogen ionizing photons and the intergalactic medium clumping factor, we find that to fully reionize the universe by redshift z~6 the population of star-forming galaxies at redshifts z~7-9 likely must extend in luminosity below the UDF12 limits to absolute UV magnitudes of M_UV\sim -13 or fainter. Moreover, low levels of star formation extending to redshifts z~15-25, as suggested by the normal UV colors of z\simeq7-8 galaxies and the smooth decline in abundance with redshift observed by UDF12 to z\simeq10, are additionally likely required to reproduce the optical depth to electron scattering inferred from CMB observations.Comment: Version accepted by ApJ (originally submitted Jan 5, 2013). The UDF12 website can be found at http://udf12.arizona.ed